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1.
Clin Chem ; 67(4): 672-683, 2021 03 31.
Article in English | MEDLINE | ID: covidwho-1165392

ABSTRACT

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.


Subject(s)
/methods , Laboratories , Mobile Health Units , Pathology, Molecular/methods , RNA, Viral/analysis , Adult , Automobiles , /instrumentation , Female , Humans , Lab-On-A-Chip Devices , Male , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Middle East Respiratory Syndrome Coronavirus/chemistry , Molecular Diagnostic Techniques/instrumentation , Molecular Diagnostic Techniques/methods , Pandemics , Pathology, Molecular/instrumentation , Robotics , /chemistry
2.
PLoS One ; 16(3): e0249231, 2021.
Article in English | MEDLINE | ID: covidwho-1154085

ABSTRACT

BACKGROUND: To date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in COVID-19 patients in the Netherlands, considering recovery as a competing risk. METHODS: In this observational multicenter cohort study we included adults with PCR-confirmed SARS-CoV-2 infection that were admitted to one of five hospitals in the Netherlands (March to May 2020). We performed a competing risk survival analysis, presenting cause-specific hazard ratios (HRCS) for the effect of preselected factors on the absolute risk of death and recovery. RESULTS: 1,006 patients were included (63.9% male; median age 69 years, IQR: 58-77). Patients were hospitalized for a median duration of 6 days (IQR: 3-13); 243 (24.6%) of them died, 689 (69.9%) recovered, and 74 (7.4%) were censored. Patients with higher age (HRCS 1.10, 95% CI 1.08-1.12), immunocompromised state (HRCS 1.46, 95% CI 1.08-1.98), who used anticoagulants or antiplatelet medication (HRCS 1.38, 95% CI 1.01-1.88), with higher modified early warning score (MEWS) (HRCS 1.09, 95% CI 1.01-1.18), and higher blood LDH at time of admission (HRCS 6.68, 95% CI 1.95-22.8) had increased risk of death, whereas fever (HRCS 0.70, 95% CI 0.52-0.95) decreased risk of death. We found no increased mortality risk in male patients, high BMI or diabetes. CONCLUSION: Our competing risk survival analysis confirms specific risk factors for COVID-19 mortality in a the Netherlands, which can be used for prediction research, more intense in-hospital monitoring or prioritizing particular patients for new treatments or vaccination.


Subject(s)
/diagnosis , Hospital Mortality , Aged , Anticoagulants/therapeutic use , Body Mass Index , /virology , Cohort Studies , Diabetes Complications , Female , Humans , Immunocompromised Host , L-Lactate Dehydrogenase/biosynthesis , Length of Stay , Male , Middle Aged , Netherlands , Proportional Hazards Models , RNA, Viral/analysis , Risk Factors , /isolation & purification , Survival Analysis
3.
PLoS One ; 16(3): e0248783, 2021.
Article in English | MEDLINE | ID: covidwho-1150546

ABSTRACT

BACKGROUND: COVID-19 test sensitivity and specificity have been widely examined and discussed, yet optimal use of these tests will depend on the goals of testing, the population or setting, and the anticipated underlying disease prevalence. We model various combinations of key variables to identify and compare a range of effective and practical surveillance strategies for schools and businesses. METHODS: We coupled a simulated data set incorporating actual community prevalence and test performance characteristics to a susceptible, infectious, removed (SIR) compartmental model, modeling the impact of base and tunable variables including test sensitivity, testing frequency, results lag, sample pooling, disease prevalence, externally-acquired infections, symptom checking, and test cost on outcomes including case reduction and false positives. FINDINGS: Increasing testing frequency was associated with a non-linear positive effect on cases averted over 100 days. While precise reductions in cumulative number of infections depended on community disease prevalence, testing every 3 days versus every 14 days (even with a lower sensitivity test) reduces the disease burden substantially. Pooling provided cost savings and made a high-frequency approach practical; one high-performing strategy, testing every 3 days, yielded per person per day costs as low as $1.32. INTERPRETATION: A range of practically viable testing strategies emerged for schools and businesses. Key characteristics of these strategies include high frequency testing with a moderate or high sensitivity test and minimal results delay. Sample pooling allowed for operational efficiency and cost savings with minimal loss of model performance.


Subject(s)
/economics , /diagnosis , /virology , Cost-Benefit Analysis , Delayed Diagnosis , Humans , Mass Screening/economics , Prevalence , RNA, Viral/analysis , RNA, Viral/metabolism , /isolation & purification , Schools , Sensitivity and Specificity
4.
Anal Chem ; 93(13): 5365-5370, 2021 04 06.
Article in English | MEDLINE | ID: covidwho-1147379

ABSTRACT

Tests for COVID-19 generally measure SARS-CoV-2 viral RNA from nasal swabs or antibodies against the virus from blood. It has been shown, however, that both viral particles and antibodies against those particles are present in saliva, which is more accessible than both swabs and blood. We present methods for highly sensitive measurements of both viral RNA and antibodies from the same saliva sample. We developed an efficient saliva RNA extraction method and combined it with an ultrasensitive antibody test based on single molecule array (Simoa) technology. We apply our test to the saliva of patients who presented to the hospital with COVID-19 symptoms, some of whom tested positive with a conventional RT-qPCR nasopharyngeal swab test. We demonstrate that combining viral RNA detection by RT-qPCR with antibody detection by Simoa identifies more patients as infected than either method alone. Our results demonstrate the utility of combining viral RNA and antibody testing from saliva, a single easily accessible biofluid.


Subject(s)
Antibodies, Viral/analysis , /diagnosis , RNA, Viral/analysis , Saliva/immunology , /virology , Female , Humans , Limit of Detection , Male , Real-Time Polymerase Chain Reaction , Reproducibility of Results , /immunology
5.
Clin Rev Allergy Immunol ; 59(1): 89-100, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1139384

ABSTRACT

The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.


Subject(s)
Antibodies, Viral/immunology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , RNA, Viral/analysis , Algorithms , Betacoronavirus/immunology , Critical Pathways , Early Diagnosis , Evidence-Based Practice , False Negative Reactions , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Medical History Taking , Pandemics , Patient Isolation , Quarantine , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Serologic Tests/methods , Severity of Illness Index , Tomography, X-Ray Computed
6.
J Med Microbiol ; 70(3)2021 Mar.
Article in English | MEDLINE | ID: covidwho-1140049

ABSTRACT

In this work, we studied the profile of IgM and IgG antibody responses to SARS-CoV-2 in 32 patients with COVID-19 from day 1 to day 24. IgM remained measurable for a much shorter period than IgG, suggesting that IgG antibody may represent the primary immune response.


Subject(s)
Antibodies, Viral/blood , /immunology , Adult , Aged , /immunology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Kinetics , Male , Middle Aged , Phosphoproteins/immunology , RNA, Viral/analysis , /isolation & purification , Spike Glycoprotein, Coronavirus/immunology
7.
Epidemiol Infect ; 149: e67, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1137722

ABSTRACT

The possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission by fomites or environmental surfaces has been suggested. It is unclear if SARS-CoV-2 can be detected in outdoor public areas. The objective of the current study was to assess the presence of SARS-CoV-2 in environmental samples collected at public playgrounds and water fountains, in a country with high disease prevalence. Environmental samples were collected from six cities in central Israel. Samples were collected from drinking fountains and high-touch recreational equipment at playgrounds. Sterile pre-moistened swabs were used to collect the samples, put in viral transfer media and transferred to the laboratory. Viral detection was achieved by real-time reverse transcriptase-polymerase chain reaction, targeting four genes. Forty-three samples were collected from playground equipment and 25 samples from water fountains. Two of the 43 (4.6%) samples from playground equipment and one (4%) sample from a drinking fountain tested positive. It is unclear whether the recovery of viral RNA on outdoor surfaces also indicates the possibility of acquiring the virus. Adherence to environmental and personal hygiene in urban settings seems prudent.


Subject(s)
/transmission , Equipment Contamination/statistics & numerical data , Parks, Recreational , Play and Playthings , RNA, Viral/analysis , /genetics , Drinking Water , Humans , Israel , Reverse Transcriptase Polymerase Chain Reaction
8.
Open Heart ; 8(1)2021 03.
Article in English | MEDLINE | ID: covidwho-1136107

ABSTRACT

OBJECTIVES: The clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK. METHODS: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention. RESULTS: Mean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for. CONCLUSION: Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.


Subject(s)
/epidemiology , Cardiovascular Diseases/epidemiology , Pandemics , Aged , Comorbidity , Female , Hospital Mortality/trends , Humans , Incidence , London , Male , RNA, Viral/analysis , Retrospective Studies , Survival Rate/trends
9.
Virol J ; 18(1): 53, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1127714

ABSTRACT

INTRODUCTION: The sudden arrival of the COVID-19 pandemic placed significant stresses on supply chains including viral transport medium (VTM). The VTM that was urgently required needed to support viral replication, as well as other routine diagnostic approaches. We describe the preparation and validation testing of VTM for rapidly expanding diagnostic testing, where the capacity of the VTM to preserve viral integrity, for culture, isolation and full sequence analysis, was maintained. METHODS: VTM was prepared using different methods of sterilization then 'spiked' with virus. The VTM was investigated using viral culture in Vero cells, and for nucleic acid detection by quantitative PCR. RESULTS: The best results were obtained by filter and autoclave-based sterilization. The VTM proved robust for culture-based analyses provided the inoculated VTM was stored at 4 °C, and tested within 48 h. The filtered VTM also supported PCR-based diagnosis for at least 5 days when the mock inoculated VTM was held at room temperature. DISCUSSION: The manual handling of VTM production, including filling and sterilization, was optimized. SARS-CoV-2 was spiked into VTM to assess different sterilization methods and measure the effects of storage time and temperature upon VTM performance. While most diagnostic protocols will not require replication competent virus, the use of high quality VTM will allow for the next phase of laboratory analysis in the COVID-19 pandemic, including drug and antibody susceptibility analysis of re-isolated SARS-CoV-2, and for the testing of vaccine escape mutants.


Subject(s)
/diagnosis , Specimen Handling/methods , Animals , Anti-Bacterial Agents/pharmacology , Cell Line , Chlorocebus aethiops , Culture Media/chemistry , Humans , RNA, Viral/analysis , Vero Cells
10.
Epidemiol Infect ; 149: e62, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1127117

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a newly emerged disease with various clinical manifestations and imaging features. The diagnosis of COVID-19 depends on a positive nucleic acid amplification test by real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the clinical manifestations and imaging features of COVID-19 are non-specific, and nucleic acid test for SARS-CoV-2 can have false-negative results. It is presently believed that detection of specific antibodies to SARS-CoV-2 is an effective screening and diagnostic indicator for SARS-CoV-2 infection. Thus, a combination of nucleic acid and specific antibody tests for SARS-CoV-2 will be more effective to diagnose COVID-19, especially to exclude suspected cases.


Subject(s)
/diagnosis , Pneumonia, Bacterial/diagnosis , /isolation & purification , Adult , Anti-Bacterial Agents/therapeutic use , Antibodies, Viral/blood , Antibodies, Viral/immunology , /pathology , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/pathology , RNA, Viral/analysis , RNA, Viral/genetics , /immunology , Treatment Outcome , Young Adult
11.
Sci Rep ; 11(1): 5372, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1123151

ABSTRACT

Wastewater-based epidemiology (WBE) is a great approach that enables us to comprehensively monitor the community to determine the scale and dynamics of infections in a city, particularly in metropolitan cities with a high population density. Therefore, we monitored the time course of the SARS-CoV-2 RNA concentration in raw sewage in the Frankfurt metropolitan area, the European financial center. To determine the SARS-CoV-2 RNA concentration in sewage, we continuously collected 24 h composite samples twice a week from two wastewater treatment plant (WWTP) influents (Niederrad and Sindlingen) serving the Frankfurt metropolitan area and performed RT-qPCR analysis targeting three genes (N gene, S gene, and ORF1ab gene). In August, a resurgence in the SARS-CoV-2 RNA load was observed, reaching 3 × 1013 copies/day, which represented similar levels compared to April with approx. 2 × 1014 copies/day. This corresponds to a continuous increase again in COVID-19 cases in Frankfurt since August, with an average of 28.6 incidences, compared to 28.7 incidences in April. Different temporal dynamics were observed between different sampling points, indicating local dynamics in COVID-19 cases within the Frankfurt metropolitan area. The SARS-CoV-2 RNA load to the WWTP Niederrad ranged from approx. 4 × 1011 to 1 × 1015 copies/day, the load to the WWTP Sindlingen from approx. 1 × 1011 to 2 × 1014 copies/day, which resulted in a preceding increase in these loading in July ahead of the weekly averaged incidences. The study shows that WBE has the potential as an early warning system for SARS-CoV-2 infections and a monitoring system to identify global hotspots of COVID-19.


Subject(s)
Environmental Monitoring , RNA, Viral/analysis , Waste Water/virology , /epidemiology , Cities , Epidemiological Monitoring , Genes, Viral , Germany , Sewage/virology , Time Factors , Viral Load , Water Purification
12.
ACS Sens ; 6(3): 1086-1093, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1120724

ABSTRACT

The outbreak of COVID-19 caused a worldwide public health crisis. Large-scale population screening is an effective means to control the spread of COVID-19. Reverse transcription-polymerase chain reaction (RT-qPCR) and serology assays are the most available techniques for SARS-CoV-2 detection; however, they suffer from either less sensitivity and accuracy or low instrument accessibility for screening. To balance the sensitivity, specificity, and test availability, here, we developed enhanced colorimetry, which is termed as a magnetic pull-down-assisted colorimetric method based on the CRISPR/Cas12a system (M-CDC), for SARS-CoV-2 detection. By this method, SARS-CoV-2 RNA from synthetic sequences and cultured viruses can be detected by the naked eye based on gold nanoparticle (AuNP) probes, with a detection limit of 50 RNA copies per reaction. With CRISPR/Cas12a-assisted detection, SARS-CoV-2 can be specifically distinguished from other closely related viruses. M-CDC was further used to analyze 41 clinical samples, whose performance was 95.12%, consistent with that of an approved Clinical RT-qPCR Diagnosis kit. The developed M-CDC method is not dependent on sophisticated instruments, which makes it potentially valuable to be applied for SARS-CoV-2 screening under poor conditions.


Subject(s)
/methods , RNA, Viral/analysis , /genetics , Bacterial Proteins , CRISPR-Associated Proteins , CRISPR-Cas Systems , Cell Line, Tumor , Colorimetry , DNA/chemistry , DNA Probes , Endodeoxyribonucleases , Gold/chemistry , Humans , Metal Nanoparticles/chemistry
13.
Int J Mol Sci ; 22(5)2021 Feb 28.
Article in English | MEDLINE | ID: covidwho-1120492

ABSTRACT

Although molecular testing, and RT-qPCR in particular, has been an indispensable component in the scientific armoury targeting SARS-CoV-2, there are numerous falsehoods, misconceptions, assumptions and exaggerated expectations with regards to capability, performance and usefulness of the technology. It is essential that the true strengths and limitations, although publicised for at least twenty years, are restated in the context of the current COVID-19 epidemic. The main objective of this commentary is to address and help stop the unfounded and debilitating speculation surrounding its use.


Subject(s)
/methods , /virology , Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction/methods , /isolation & purification , Clinical Laboratory Techniques/methods , Humans , RNA, Viral/analysis , RNA, Viral/genetics , Sensitivity and Specificity
14.
J Coll Physicians Surg Pak ; 30(1): S26-S28, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1112944

ABSTRACT

We present a case of coronavirus disease 2019 (COVID-19) re-infection where the time interval between two COVID-positive episodes is the longest in the literature. A 40-year male patient was admitted to the Emergency Department with  complaints of sore throat, cough and diarrhea; and was re-diagnosed as COVID-19 positive after a virus-free period. He did not have a chronic disease in his anamnesis and used no medication. After COVID-19 infection and a long recovery period, he became COVID-19 positive again. In this case, the time to second COVID-19 infection was 94 days from the first positive PCR test and 86 days from the complete resolution of symptoms. This is one of the longest COVID-19-free period between two episodes of infection in the literature. Key Words: COVID-19, Recurrence, Re-infection, Recovery.


Subject(s)
/epidemiology , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , /genetics , Adult , /virology , Humans , Male , Pandemics , Recurrence
16.
Nature ; 592(7852): 122-127, 2021 04.
Article in English | MEDLINE | ID: covidwho-1104508

ABSTRACT

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.


Subject(s)
/transmission , Mutation , /physiology , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , /genetics , Animals , Bronchi/cytology , Bronchi/virology , Cell Line , Cells, Cultured , Cricetinae , Disease Models, Animal , Epithelial Cells/virology , Female , Ferrets/virology , Founder Effect , Gene Knock-In Techniques , Genetic Fitness , Humans , Male , Mesocricetus , Mice , Nasal Mucosa/cytology , Nasal Mucosa/virology , Protein Binding , RNA, Viral/analysis , /metabolism , /pathogenicity
18.
Nature ; 592(7853): 283-289, 2021 04.
Article in English | MEDLINE | ID: covidwho-1101660

ABSTRACT

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).


Subject(s)
/immunology , /prevention & control , Disease Models, Animal , /immunology , Aging/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, Viral/chemistry , Antigens, Viral/genetics , Antigens, Viral/immunology , /therapy , /administration & dosage , /genetics , Cell Line , Clinical Trials as Topic , Female , Humans , Immunization, Passive , Internationality , Macaca mulatta/immunology , Macaca mulatta/virology , Male , Mice , Mice, Inbred BALB C , Models, Molecular , Protein Multimerization , RNA, Viral/analysis , Respiratory System/immunology , Respiratory System/virology , /genetics , Solubility , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Vaccination , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
19.
Indian J Ophthalmol ; 69(3): 773-774, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1089043

ABSTRACT

With increasing experience, it has been suggested that the SARS-CoV-2 virus has a neurotropic effect. Here, we present a case of a tonic pupil who developed after COVID-19 infection. A 36-year-old woman presented with progressive photophobia and blurred vision. On neurological examination, loss of deep tendon reflexes accompanying a tonic pupil was detected and brain MR imaging was normal. With this case, we aimed to describe a rare pattern of neurological involvement caused by the possible SARS-CoV-2 virus.


Subject(s)
Adie Syndrome/diagnosis , /complications , Adie Syndrome/etiology , Adult , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , RNA, Viral/analysis , /genetics
20.
Anal Chim Acta ; 1154: 338330, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1086723

ABSTRACT

The recent outbreak of coronavirus disease 2019 (COVID-19) is highly infectious, which threatens human health and has received increasing attention. So far, there is no specific drug or vaccine for COVID-19. Therefore, it is urgent to establish a rapid and sensitive early diagnosis platform, which is of great significance for physical separation of infected persons after rapid diagnosis. Here, we propose a colorimetric/SERS/fluorescence triple-mode biosensor based on AuNPs for the fast selective detection of viral RNA in 40 min. AuNPs with average size of 17 nm were synthesized, and colorimetric, surface enhanced Raman scattering (SERS), and fluorescence signals of sensors are simultaneously detected based on their basic aggregation property and affinity energy to different bio-molecules. The sensor achieves a limit detection of femtomole level in all triple modes, which is 160 fM in absorbance mode, 259 fM in fluorescence mode, and 395 fM in SERS mode. The triple-mode signals of the sensor are verified with each other to make the experimental results more accurate, and the capacity to recognize single-base mismatch in each working mode minimizes the false negative/positive reading of SARS-CoV-2. The proposed sensing platform provides a new way for the fast, sensitive, and selective detection of COVID-19 and other diseases.


Subject(s)
Biosensing Techniques/methods , Metal Nanoparticles/chemistry , RNA, Viral/analysis , /genetics , /virology , Gold/chemistry , Humans , Limit of Detection , Particle Size , RNA, Viral/chemistry , Spectrum Analysis, Raman , Spike Glycoprotein, Coronavirus/genetics
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